Abstract
BackgroundAsbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. We evaluated the potential diagnostic biomarkers for these diseases.MethodsThe serum concentrations of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinase-2 (MMP-2), MMP-7, and MMP-9 were measured in 43 patients with asbestosis, 45 patients with silicosis, 40 dust-exposed workers (DEWs) without pneumoconiosis, and 45 healthy controls (HCs). Chest high-resolution computed tomography (HRCT) images were reviewed by experts blinded to the clinical data. According to the receiver operating characteristic (ROC) curve, the ideal level of each biomarker and its diagnostic sensitivity were obtained.ResultsThe serum KL-6 and MMP-2 concentrations were highest in patients with asbestosis, particularly in comparison with those in DEWs and HCs (P<0.05). The serum SP-D concentration was significantly higher in patients with asbestosis than in patients with silicosis, DEWs, and HCs (P<0.01), whereas no significant difference was noted among patients with silicosis, DEWs, and HCs. No significant difference in the serum MMP-7 or -9 concentration was found among patients with asbestosis, patients with silicosis, DEWs, or HCs. Among patients with asbestosis, the serum KL-6 concentration was significantly correlated with the lung fibrosis scores on HRCT and negatively correlated with the forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted. The serum SP-D and MMP-2 concentrations were negatively correlated with the DLCO % predicted (all P<0.05). The order of diagnostic accuracy according to the ROC curve was KL-6, SP-D, and MMP-2 in patients with asbestosis alone and in the combination of both patients with asbestosis and those with silicosis. The combination of all three biomarkers may increase the possibility of diagnosing asbestosis (sensitivity, 93%; specificity, 57%) and both asbestosis and silicosis (sensitivity, 83%; specificity, 62%).ConclusionsKL-6, SP-D, and MMP-2 are available biomarkers for the adjuvant diagnosis of asbestosis and silicosis. The combination of all three biomarkers may improve the diagnostic sensitivity for asbestosis and silicosis.
Highlights
Asbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust
In the present study, we showed that the diagnostic value of the serum biomarkers Krebs von den Lungen 6 (KL-6), surfactant protein D (SP-D), and Matrix metalloproteinase (MMP)-2 was higher in patients with asbestosis or patients with silicosis than in dust-exposed workers (DEWs) and healthy controls (HCs)
The serum KL-6 concentration was significantly correlated with the lung fibrosis scores on highresolution computed tomography (HRCT) while negatively correlated with the forced vital capacity (FVC) % predicted and DLCO % predicted
Summary
We evaluated the potential diagnostic biomarkers for these diseases. Asbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. China, where the asbestos and silica exposure industries have not been greatly limited, has invariably exhibited a sustained epidemic of asbestosis and silicosis [3, 4]. Biomarkers with which to detect these pneumoconioses other than imaging and lung function testing are warranted [5]. Krebs von den Lungen 6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinases (MMPs) are potential biomarkers for diagnosing and monitoring progression of various fibrotic lung diseases
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